Down but Not Out: The Role of MicroRNAs in Hibernating Bats.

MicroRNAs (miRNAs) regulate many physiological processes through post-transcriptional control of gene expression and are a major part of the small noncoding RNAs (snRNA). As hibernators can survive at low body temperatures (Tb) for many months without suffering tissue damage, understanding the mechanisms that enable them to do so are of medical interest. Because the brain integrates peripheral physiology and white adipose tissue (WAT) is the primary energy source during hibernation, we hypothesized that both of these organs play a crucial role in hibernation, and thus, their activity would be relatively increased during hibernation. We carried out the first genomic analysis of small RNAs, specifically miRNAs, in the brain and WAT of a hibernating bat (Myotis ricketti) by comparing deeply torpid with euthermic individual bats using high-throughput sequencing (Solexa) and qPCR validation of expression levels. A total of 196 miRNAs (including 77 novel bat-specific miRNAs) were identified, and of these, 49 miRNAs showed significant differences in expression during hibernation, including 33 in the brain and 25 in WAT (P≤0.01 &│logFC│≥1). Stem-loop qPCR confirmed the miRNA expression patterns identified by Solexa sequencing. Moreover, 31 miRNAs showed tissue- or state-specific expression, and six miRNAs with counts >100 were specifically expressed in the brain. Putative target gene prediction combined with KEGG pathway and GO annotation showed that many essential processes of both organs are significantly correlated with differentially expressed miRNAs during bat hibernation. This is especially evident with down-regulated miRNAs, indicating that many physiological pathways are altered during hibernation. Thus, our novel findings of miRNAs and Interspersed Elements in a hibernating bat suggest that brain and WAT are active with respect to the miRNA expression activity during hibernation.